AusPAR: Ivabradine - Therapeutic Goods Administration

Other studies
Not applicable.
Electrocardiograph
Pivotal studies
AusPAR Coralan Ivabradine Servier Laboratories (Australia) Pty Ltd PM-2010-03269-3-3
Final 31 October 2012
Therapeutic Goods Administration
Electrocardiograms were taken to detect the lowest heart rate on treatment present in
patients on the Safety Set. An on-treatment recording of HR < 40 bpm was reported in
0.3% (10/3178) of patients in the ivabradine group versus 0.1% (3/ 3209) in the placebo
group. An on-treatment recording of HR < 50 bpm was reported in 21.3% (676/ 3178) of
patients in the ivabradine group versus 2.2% (70/ 3209) in the placebo group.
Overall, the proportion of patients with asymptomatic bradycardia that led to study drug
discontinuation was 0.9% and 0.2% in the ivabradine and placebo groups, respectively,
and that for symptomatic bradycardia was 0.6% and 0.2%, respectively. Asymptomatic
bradycardia that was considered treatment-related SAEs occurred in 0.1% and 0% in the
ivabradine and placebo groups, respectively. Symptomatic bradycardia that was
considered treatment-related SAEs occurred in 0.4% and < 0.1% in the ivabradine and
placebo groups, respectively.
Other studies
Not applicable.
Vital signs
Pivotal studies
Sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured at
each scheduled visit during the study. There was a small increase in mean sitting SBP
between baseline and last value on treatment in both treatment groups (mean change ±
SD of + 4.1 ± 16.0 mmHg in the ivabradine group and +2.0 ± 16.2 mmHg in the placebo
group).
There was minimal change in mean sitting DBP between baseline and last value on
treatment in both treatment groups (mean change ± SD of +0.4 ± 10.2 mmHg in the
ivabradine group and +0.7 ± 10.3 mmHg in the placebo group).
Other studies
Not applicable.
Postmarketing experience
No postmarketing data was provided. The proposed PI contains data regarding
postmarketing experience, which is unamended from the currently approved PI and states
that “The following adverse reactions (frequency unknown) have been reported in
postmarketing use with ivabradine; rash, erythema, pruritis, hypotension, malaise,
syncope (possibly linked to bradycardia).”
Other safety issues
Safety in special populations
In the subgroup of patients aged ≥ 75 years (N = 720, n=367 in ivabradine group, n=353 in
the placebo group), the incidence of TEAEs was comparable between the ivabradine group
and the placebo group (78.8%, 50.3%PY versus 77.6%, 48.0%PY, respectively) (Table 16).
The most frequently reported TEAEs by SOC were Cardiac disorders (50.1%, 32.0%PY
versus 47.3%, 29.2%PY, respectively), Infections and infestations (26.2%, 16.7%PY versus
26.1%, 16.1%PY, respectively) and Vascular disorders (13.9%, 8.9%PY versus 14.2%,
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